Michalska Patrycja, León Rafael
Instituto Teófilo Hernando y Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
Antioxidants (Basel). 2020 Aug 12;9(8):740. doi: 10.3390/antiox9080740.
Neurodegenerative diseases are characterized by a progressive loss of neurons in the brain or spinal cord that leads to a loss of function of the affected areas. The lack of effective treatments and the ever-increasing life expectancy is raising the number of individuals affected, having a tremendous social and economic impact. The brain is particularly vulnerable to oxidative damage given the high energy demand, low levels of antioxidant defenses, and high levels of metal ions. Driven by age-related changes, neurodegeneration is characterized by increased oxidative stress leading to irreversible neuronal damage, followed by cell death. Nevertheless, neurodegenerative diseases are known as complex pathologies where several mechanisms drive neuronal death. Herein we discuss the interplay among oxidative stress, proteinopathy, and neuroinflammation at the early stages of neurodegenerative diseases. Finally, we discuss the use of the Nrf2-ARE pathway as a potential therapeutic strategy based on these molecular mechanisms to develop transformative medicines.
神经退行性疾病的特征是大脑或脊髓中的神经元进行性丧失，导致受影响区域功能丧失。由于缺乏有效的治疗方法以及预期寿命的不断增加，受影响的个体数量正在上升，产生了巨大的社会和经济影响。鉴于大脑对能量的高需求、抗氧化防御水平低以及金属离子水平高，大脑特别容易受到氧化损伤。在与年龄相关的变化的驱动下，神经退行性变的特征是氧化应激增加，导致不可逆的神经元损伤，随后细胞死亡。然而，神经退行性疾病是已知的复杂病理，其中多种机制驱动神经元死亡。在此，我们讨论神经退行性疾病早期氧化应激、蛋白病和神经炎症之间的相互作用。最后，我们基于这些分子机制讨论使用Nrf2-ARE途径作为一种潜在的治疗策略来开发变革性药物。
